1-151406100-G-A
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015100.4(POGZ):c.2935C>T(p.Arg979Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Consequence
POGZ
NM_015100.4 stop_gained
NM_015100.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 3.51
Genes affected
POGZ (HGNC:18801): (pogo transposable element derived with ZNF domain) The protein encoded by this gene appears to be a zinc finger protein containing a transposase domain at the C-terminus. This protein was found to interact with the transcription factor SP1 in a yeast two-hybrid system. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 41 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-151406100-G-A is Pathogenic according to our data. Variant chr1-151406100-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 218149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-151406100-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POGZ | NM_015100.4 | c.2935C>T | p.Arg979Ter | stop_gained | 19/19 | ENST00000271715.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POGZ | ENST00000271715.7 | c.2935C>T | p.Arg979Ter | stop_gained | 19/19 | 1 | NM_015100.4 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome Pathogenic:5
Pathogenic, no assertion criteria provided | clinical testing | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Nov 10, 2015 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | May 06, 2019 | The POGZ c.2935C>T (p.Arg979Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Arg979Ter variant has been reported in one study in which it is found in one individual in a heterozygous state (White et al. 2016). The individual's phenotype included global developmental delay, short stature, microcephaly, hypotonia, brachycephaly, high arched palate, sensorineural hearing loss, exotropia, optic nerve hypoplasia, and rod-cone retinal dystrophy. The p.Arg979Ter variant is not found in the Genome Aggregation Database in a region of good sequence coverage, so the variant is presumed to be rare. Based on the potential impact of truncating variants, absence from population frequency databases, and identification in a de novo state, the p.Arg979Ter variant is classified as pathogenic for White-Sutton syndrome. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 06, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 14, 2021 | - - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 01, 2014 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 14, 2023 | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 432 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26739615, 37016333, 25533962) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;D;D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at